Funding sources: American Cancer Society, The Ohio State University, Virginia Commonwealth University

Researchers are employing leading-edge computational chemistry to uncover how a particular set of enzyme reactions helps metabolize therapeutic drugs in the human body. They believe a better understanding may lead to the ability to transform environmental pollutants into easily biodegradable substances.

Christopher Hadad, professor of chemistry at The Ohio State University, and John Hackett, an assistant professor of medicinal chemistry at Virginia Commonwealth University, are studying Cytochrome P450 (CYP) enzymes. These enzymes, when activated by oxygen, help create natural products, steroid hormones, and eicosanoids –molecules critical to the chemical breakdown of most medications.

“A significant fraction of drug candidates are disqualified from further development as a result of undesirable interaction with, or extensive metabolism by, CYP enzymes,” said Hadad. “Favorable outcomes from this approach should provide the proof-of-principle of these techniques to address catalytic mechanisms of other CYP-catalyzed reactions of biomedical importance.”

“CYP enzymes utilize a few very reactive, short-lived intermediates to catalyze a large number of reactions that are extremely difficult to study experimentally,” said Hackett. “The computational resources at OSC allow us to investigate them in molecular detail, providing insight that can be harnessed for safer drug design.”